The effect of nutrition on host defenses against infection has major importance for health in the United States. We showed that one nutritional abnormality, acute starvation, enhanced resistance of mice to Listeria monocytogenes. It appeared that increased macrophage activity - induced by starvation - may have been responsible for this phenomenon. We also explored the relevance of these findings to humans by studying volunteers, who were starved for 14 days. We found that immune effectors, including peripheral blood monocytes, had increased activity during starvation. In this project, we will investigate the mechanism for the increased resistance and altered macrophage function in an animal model. The role of fixed tissue macrophages in resistance of starved mice will be investigated first. The function of these cells will be assayed by an in vivo phagocytic assay, by early (first 12 hours) growth curves of intracellular pathogens, and by blocking macrophage function with dextran and carrageenan. Serum factors as potential stimulators of macrophage function and the effect of starvation on alveolar macrophages will also be investigated. The role of bone marrow-derived, circulating monocytes will then be tested by measurung alterations in the production of monocytes by bone marrow and spleen. This will be accomplished by determining the number of bone marrow and spleen stem cells in a monocyte/macrophage colony assay, the serum concentrations of CSF, and the effect of blocking CSF with the rabbit anti-CSF serum. In addition, the effect of radiation and Sr89 and the histopathological changes in the reticuloendothelial system will be measured in starved and fed mice. The experiments in this project will characterize in an experimental model how short-term starvation affects macrophage and monocyte function and as a result, resistance to infection. This work may lead to additional studies on the effect of specific nutrients on the macrophage/monocyte axis. These studies also should increase our understanding of the interrelation between diet and aimmune function and may suggest new methods for manipulating the immune system beneficially.
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